Laser Acupuncture for Chronic Migraine: Clinical Response, Traditional Chinese Medicine Syndrome Patterns, and Brain Function (PRISM-CM)

实验性的：Chronic Migraine: Active Laser Acupuncture

设备：810 nm laser acupuncture

Participants will receive noninvasive laser acupuncture using an 810-nm near-infrared laser with an output power of 150 mW. Laser irradiation will be applied to 13 standardized acupoints: bilateral Fengchi (GB20), Shuaigu (GB8), Taiyang (EX-HN5), Zanzhu (BL2), Hegu (LI4), Taichong (LR3), and unilateral Yintang (EX-HN3). Each acupoint will be irradiated for 30 seconds, delivering 4.5 J of energy per point. Treatment will be administered twice weekly for four consecutive weeks, for a total of eight sessions. The same standardized treatment protocol will be used for participants with chronic migraine assigned to the active laser acupuncture group and healthy volunteers receiving active laser acupuncture.

假比较器：Chronic Migraine: Sham Laser Acupuncture

设备：Sham Laser Acupuncture

Participants assigned to the sham laser acupuncture group will undergo a procedure identical to active laser acupuncture, using the same laser device, standardized acupoints, treatment duration, and operating procedures, but without emission of therapeutic laser energy. The sham procedure will target the same 13 acupoints: bilateral Fengchi (GB20), Shuaigu (GB8), Taiyang (EX-HN5), Zanzhu (BL2), Hegu (LI4), Taichong (LR3), and unilateral Yintang (EX-HN3). Each acupoint will be treated for 30 seconds. Sham treatment will be administered twice weekly for four consecutive weeks, for a total of eight sessions. The procedure is designed to maintain participant blinding and serve as a placebo control for active laser acupuncture.

实验性的：Healthy Volunteers: Active Laser Acupuncture

设备：810 nm laser acupuncture

Participants will receive noninvasive laser acupuncture using an 810-nm near-infrared laser with an output power of 150 mW. Laser irradiation will be applied to 13 standardized acupoints: bilateral Fengchi (GB20), Shuaigu (GB8), Taiyang (EX-HN5), Zanzhu (BL2), Hegu (LI4), Taichong (LR3), and unilateral Yintang (EX-HN3). Each acupoint will be irradiated for 30 seconds, delivering 4.5 J of energy per point. Treatment will be administered twice weekly for four consecutive weeks, for a total of eight sessions. The same standardized treatment protocol will be used for participants with chronic migraine assigned to the active laser acupuncture group and healthy volunteers receiving active laser acupuncture.

Change From Baseline in Monthly Migraine Days (MMD) at Week 12

Monthly migraine days (MMD) will be calculated from daily headache diaries over a 28-day period. Change from baseline will be calculated as MMD at Week 12 minus baseline MMD. Negative values indicate a reduction in migraine frequency. The unit of measurement is days per 28 days.

Change in Monthly Headache Days (MHD) From Baseline to Week 12

Monthly headache days (MHD) will be calculated from daily headache diaries as the number of days with headache during a 28-day period. Change from baseline will be calculated as the Week 12 value minus the baseline value. Negative values indicate fewer headache days. The unit of measurement is days per 28 days.

Change in Acute Medication Days (AMD) From Baseline to Week 12

Acute medication days (AMD) will be defined as the number of days on which participants use acute medication for headache or migraine during a 28-day period, as recorded in daily headache diaries. Change from baseline will be calculated as the Week 12 value minus the baseline value. Negative values indicate reduced acute medication use. The unit of measurement is days per 28 days.

Change in Headache Pain Intensity From Baseline to Week 12

Headache pain intensity will be assessed using an 11-point Numerical Rating Scale (NRS), ranging from 0 (no pain) to 10 (worst imaginable pain). Higher scores indicate greater headache intensity. Change from baseline will be calculated as the Week 12 score minus the baseline score. Negative values indicate improvement.

Change in Headache Duration From Baseline to Week 12

Headache duration will be recorded in daily headache diaries and expressed as the average duration of headache episodes in hours. Change from baseline will be calculated as the Week 12 value minus the baseline value. Negative values indicate shorter headache duration.

Change in Migraine Disability Assessment (MIDAS) From Baseline to Week 12

Migraine-related disability will be assessed using the Migraine Disability Assessment (MIDAS). The total score is calculated by summing the number of days of missed or reduced activities across five items during the preceding three months. Higher scores indicate greater migraine-related disability.

Change in Hospital Anxiety and Depression Scale (HADS) From Baseline to Week 12

Emotional distress will be assessed using the Hospital Anxiety and Depression Scale (HADS). The scale comprises 14 items divided into anxiety and depression subscales, each ranging from 0 to 21. The total score ranges from 0 to 42, with higher scores indicating greater emotional distress.

Change in Beck Depression Inventory (BDI) From Baseline to Week 12

Depressive symptoms will be assessed using the Beck Depression Inventory (BDI). The total score ranges from 0 to 63, with higher scores indicating greater severity of depressive symptoms.

Change in Pittsburgh Sleep Quality Index (PSQI) Total Score From Baseline to Week 12

Sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI). The global score is calculated by summing seven component scores, each ranging from 0 to 3. The total score ranges from 0 to 21, with higher scores indicating poorer sleep quality. Change from baseline will be calculated as the Week 12 score minus the baseline score. Negative values indicate improvement.

Percentage of Participants With at Least a 50% Reduction in Monthly Migraine Days at Week 12

A migraine responder will be defined as a participant achieving at least a 50% reduction in monthly migraine days (MMD) at Week 12 compared with baseline. The outcome will be reported as the percentage of participants meeting this criterion in each treatment group. Higher percentages indicate a greater proportion of treatment responders.

Change in Regional Brain Volume Assessed by Structural MRI

Structural magnetic resonance imaging (MRI) will be used to assess longitudinal changes in regional brain volume following laser acupuncture treatment. Brain volume will be measured in cubic millimeters (mm³). Changes will be evaluated from baseline to Months 3 and 6. Higher or lower values do not necessarily indicate better or worse clinical outcomes.

Change in Resting-State Functional Connectivity Assessed by fMRI

Resting-state functional magnetic resonance imaging (fMRI) will be used to assess longitudinal changes in brain functional connectivity following laser acupuncture treatment. Functional connectivity will be quantified using Fisher's z-transformed correlation coefficients. Changes will be evaluated from baseline to Months 3 and 6. Higher or lower values indicate differences in functional connectivity and do not necessarily represent better or worse clinical outcomes.

Change in Brain Activation During Laser Acupuncture Assessed by fMRI

Task-based functional magnetic resonance imaging (fMRI) will be used to evaluate brain activation responses during laser acupuncture stimulation. Brain activation will be quantified using blood oxygen level-dependent (BOLD) signal changes, expressed as percentage signal change relative to a reference condition. Longitudinal changes will be evaluated from baseline to Months 3 and 6. Higher or lower values do not necessarily indicate better or worse clinical outcomes.

Change in White Matter Integrity Assessed by Diffusion Tensor Imaging

Diffusion tensor imaging (DTI) will be used to assess longitudinal changes in white matter microstructure following laser acupuncture treatment. White matter integrity will be evaluated using fractional anisotropy (FA), a unitless measure ranging from 0 to 1. Changes will be evaluated from baseline to Months 3 and 6. Higher FA values reflect greater directional organization of water diffusion and do not necessarily indicate better clinical outcomes.